The systemic vasculitides are a group of otherwise diverse diseases that share the characteristic of inflammatory destruction of blood vessels, with high risk of organ damage or death if untreated. With aggressive immune-suppressive treatment, most patients survive, but subsequent disease course is variable, relapse is common, and long-term morbidity from vasculitis or its treatment is expected. There is a significant need for markers of disease activity, risk of relapse, and long-term damage. For most of the vasculitides, pathophysiology is poorly understood. Thus, biological specimens can and should also be studied to identify disease-specific features, such as autoantibodies or novel microbes. The discovery of ANCA antibodies two decades ago shows the great value that such investigations can have in improving diagnostic testing and developing new treatments. The VCRC Longitudinal Studies (see Project 1 of this overall application) include collection of biological specimens at every clinical visit, so that a large repository has been created. The value of the VCRC Biospecimen Repository is evident from the interest that both VCRC and non-VCRC investigators have expressed in performing studies using this resource. The Specific Aims of this project are to: 1) continue and expand the VCRC Biomarker Discovery Program to identify novel markers of disease activity, response to treatment, and predictors of remission and relapse, in seven forms of vasculitis; 2) continue to encourage investigators inside and outside the VCRC to perform studies using VCRC clinical data and biospecimens, using well-established and streamlined procedures for review and approval of proposals and for selection and delivery of samples. 3) expand the sample collection protocol of the VCRC Longitudinal Studies to include collection of whole blood RNA and peripheral blood mononuclear cells in selected patients, to create additional opportunities to discover biomarkers, including novel microbes that may be associated with particular vasculitides or with vasculitis disease activity.